BACKGROUND: The StratifyJCV® test is a qualitative assay to classify MSers as anti-JC virus (JCV) antibody positive or negative. Quantification of anti-JCV antibody levels in serum and cerebrospinal fluid (CSF) of MSers might add to the progressive multifocal leukoencephalopathy (PML) risk assessment.OBJECTIVE: The objective of this study is to test sera of MSers in a quantitative anti-JCV antibody assay, and to compare the results with pre-existing data from the StratifyJCV® test.METHODS: Sera of a total of 175 MS MSers and matched non-MS-controls were tested for anti-JCV antibodies using glutathione S-transferase-tagged-VP1 (VP1 is a bit of the virus and the glutathione S transferase is marker protein created by molecular engineering to help produce and purify the viral VP1 protein) as antigen. Antibody reactivity was quantified in arbitrary units using human immunoglobulin as standard.

RESULTS: The comparison of our assay with StratifyJCV® showed good inter-assay agreement (kappa 0.6), and strong correlation for antibody reactivity (r(2) = 0.94). Discordant samples had low-reactive positivity, and a higher proportion (13% vs. 4%) tested positive in the StratifyJCV® test only.CONCLUSIONS: The method presented is a tool for the reliable quantification of anti-JCV antibodies, which demonstrates good agreement with results from StratifyJCV®. In contrast to StratifyJCV®, they pre-adsorbed all of the sera with BK virus (BKV) VP1 protein to reduce cross-reactivity. This step may account for a higher species-specificity in their assay. As such, their assay might be a promising additional tool for PML risk assessment.

"The new StratifyJCV assay from Biogen-Idec is more sensitive and specific than the version one of the assay and other JCV assays out there. This has resulted in quite a large number of MSers flipping from being negative to positive. These MSers tend to have low levels of antibodies suggesting they are borderline positive. In comparison MSers who become positive from being infected with JC virus from exposure to the virus tend to have high titres. This is all academic at present as we treat both these groups of MSers as being infected with the virus and therefore being at high-risk of developing PML as a complication of natalizumab treatment. However, there is some emerging data and theoretical reasons why these groups of JCV seropositive MSers may be different; the MSers who seroconvert with low titres at the lower end of the positive range may be false positives, whereas those with high titres are true seroconverters due to recent exposure to the virus. Hopefully, Biogen-Idec will be able to answer this question when they have enough data in the future. Why is this important? It may be important if you happen to one of these seroconverters and don't want to switch your treatments."

This is a relatively small study, but covers something that I have become increasingly interested in - how to predict and (more importantly) prevent falls. Unfortunately resources are limited, and an effective falls prevention strategy needs to be directed at those who will most benefit from this - i.e. those who are most likely to fall. In addition, any falls prevention strategy needs to be designed to best benefit those who are using it.

The finding that recurrent fallers have a slower cognitive processing is not a new one (see here and here). However, the lack of an effect of poor balance and mobility is in contrast to other larger studies. We also have data from the MS clinic here regarding the Berg Balance Scale and self-reported balance confidence in a larger group of people with MS (99 people) which is in contrast to these findings - they do seem to predict falls risk, albeit imperfectly.

The most striking thing about the falls literature is the fact that a large number of falls go unreported. Maybe this is learned helplessness, in that our falls strategies are not working, but it is something that we need to improve. If you are falling, then please tell your neurologist about it! It is difficult to highlight deficiencies and campaign for appropriate changes in the system without having the clinical data to back this up.

Design:Thirty six people (30 women and 6 men) diagnosed with relapsing remitting multiple sclerosis participated in two testing sessions, one week apart. Each participant performed two sequential trials of the timed 25-foot walk test per session and the walk performance was measured with a laser timing system.

Wednesday, 27 February 2013

#MSBlog: Does your neurologist belong the www.non-patronising_doctors.org? Kremenchutzky and Walt. Perceptions of Health Status in Multiple Sclerosis Patients and Their Doctors. Can J Neurol Sci. 2013 Mar ;40:210-218.Objective: To compare neurologist and MSers perceptions of multiple sclerosis (MS)-related health status. Methods: MSers (n=99) were recruited from six sites in Canada. Following a consultation with their neurologist, MSers estimated their relapse frequency, rated their general health and quality of life (QoL), reviewed descriptions of eight health domains and selected the three most important, and completed a utility assessment using the standard gamble (SG). Concurrently, neurologists independently used the same instruments to rate their MSers' health status. Assessments were compared on the basis of paired mean values of both groups and the degree of exact agreement quantified by intraclass coefficient (ICC) and kappa analyses, which yield values of 1.0 with 100% agreement.Results: There were significant differences (p<0.001) between MSers and neurologist ratings for relapses in the last year (0.86 vs. 0.4, respectively), QoL (61.2 vs. 69.7 (maximum score = 100) and utility (0.864 vs. 0.971); ICC analysis revealed moderate to poor levels of agreement (0.56 for QoL to 0.03 for SG). There was little concordance in identification of important health domain and the only significant associations were in bodily pain and social functioning (kappa statistic = 0.24, p = 0.026 for both). Neurologists identified physical functioning domains as important, while MSers placed more emphasis on mental health domains.

Conclusions: Discrepancies between neurologist and MSer perceptions of MS were observed. The study identifies a need to educate neurologists on the recognition of MS health domains that are important in the definition of MSer QoL.

"Are you surprised by the results of this study? I am not! Almost every bit of research shows a disconnect between what MSers and neurologists think and expect. This applies to the assessment of risk as well; neurologists are much more risk adverse than MSers when making decisions about DMTs and treatment strategies. When will this change? May be in the next generation! May be neurologists should all join www.non-patronising_doctors.org."

"I created www.non-patronising_doctors.org, a hypothetical organisation, to make a point in relation to concordance in a lecture I gave at the European Charcot Foundation meeting in Lisbon back in 2005. I was promoting the concept of MSer choice with regard to DMTs. I recall being verbally attacked by many neurologists in the audience at that meeting for suggesting MSers had enough knowledge to make decisions regarding their treatment. Things have clearly moved on a lot since then, but this study shows things need to move a lot further."

Background: Previous studies show that MS patients take longer than healthy controls
to plan their solutions to Tower of London (TOL) problems but yield
conflicting results regarding the quality of their solutions.

Objective: The
present study evaluated performance under untimed or timed conditions to
assess the possibility that differences in planning ability only occur
when restrictions in solution times are imposed. Methods: MS patients (n = 39)
and healthy controls (n = 43) completed a computerized version of the
TOL under one of two conditions. In the untimed condition, participants
were allowed as much time as needed on each problem. In the timed
condition, limits were imposed on solution times and time remaining was
displayed with each problem. Results: Patients exhibited longer planning times
than controls, and the disparity between groups increased with problem
difficulty. Planning performance depended upon condition. In the untimed
condition, patients and controls performed equally well. When solution
times were restricted, however, patients solved fewer problems than
controls. MS patients' planning ability is intact when permitted
sufficient time to formulate the required plan. Conclusion: Deficiencies in planning
are only evident when time is restricted, and, therefore, are more
accurately considered a relative consequence of disease-related problems
in information processing speed. (JINS, 2013, 19, 1-8).

This study looked at the time to do a problem solving test and when given unlimited time MSers did just as well as non-MSers, but when there was a time restriction, MSers were slower. So make sure you give yourself extra time.Were you aware of the issues in this post? It would be great if you could complete this survey for us so that we can find out. Thanks.

Tuesday, 26 February 2013

Objectives: To estimate average annual cost per multiple sclerosis
(MS) patient in the United States using published estimates from the
literature.

Methods: A search was performed of English-language
literature published between 2007 and June 2012 in PubMed and Embase
using the term 'multiple sclerosis'
and the subject heading 'healthcare costs'. Included articles were
primary studies with MS cost figures that could be converted to per
patient per year values. Costs were inflated to 2011 dollars using the
medical component of the Consumer Price Index.

Results: Fifteen
studies met the inclusion criteria. Eight presented only direct cost
calculations; the remaining seven presented estimates of total cost,
broken down into direct and indirect costs. Total all-cause healthcare
costs for MS as reported by studies that included direct and indirect
costs ranged from $8,528 to $54,244 per patient per year. On average,
direct costs comprised 77% (range 64-91%) of total costs. Prescription
medications accounted for the majority of direct costs. On average,
indirect costs comprised 23% (range 9-36%) of total costs. Compared with
direct all-cause medical costs for other chronic conditions reported in
the literature, MS ranked second behind congestive heart failure.
Limitations: Data sources in these studies were dated, ranging from
1999 to 2008, and therefore do not include some of the newer, more
costly therapies. In addition, this review does not include either
assessment of the decrements in quality of life associated with MS or
costs associated with increasing levels of disability or early
retirement. Furthermore, variations in study designs, populations,
methodologies, and cost inputs preclude more precise cost estimates.

Conclusions: MS is a costly chronic disease. Further research is
needed to understand: costs by MS type, costs associated with increasing
disability and early retirement, and the potential impact of new
treatments expected to launch in coming years.

As major proportion of our readers now come from the USA, this may be of interest to you. As we all can see MS is a costly disease. This data was generated from data published some time ago and the cost will have increased since then

Well that is it for this round of Question Time this time round. Maybe we will do another one.

We have to thank the panel for being brave enough to put their neck out and a special thanks for Doctor Ruth, Sir Jeremy and Ila for pitching up at short notice.

We also give special thanks to Vasilis Vasilopoulous for having the guts to participate. He did so, not knowing what we were really up or what was in store for him or his answers. We hope he feels that we were civil and gave him fair opportunities to say what he wanted.

Although this was not discussed, I think it was appropriate that we did not question this views at the time, especially as he would not be able to defend them

Question 1. Are citizen petition challenges (to the FDA) by companies in the best interest of MSers? (Q. Posted 23rd Jan 2013). Did you miss it? click here.

VV Response. "There is no way to predict. It depends on the details of each case. It might save them from a potentially dangerous drug, but it might also prohibit access to a cheap drug. In any case, it's rather disturbing to know that MSsers are being used as a weapon in the competition between companies."

Team G reposte. None we are singing from roughly the same hymn sheet. Maybe we need a pharma person on the panel next time.

Question 2.What causes liberation therapy to work for some and not for others (Q.posted 4th December 2012) and should we be researching this in the UK? (Q.posted 23rd Nov. 2012). Did you miss it? Click here.

Team G reposte. Although I think that VV and Prof G would be having a disagreement about the reality of the condition. Maybe some thought could have been given to the response and placebo effects and neuros verses MSers views on treatments. The value of the trials could have been discussed. Shame about the trollers who curtail and form of sensible discussion on this subject

VV Response.VV Response. "Drugs can be dangerous, and cost money. This question is posed because expensive drugs of limited efficacy and great danger can get approved in absence of any other treatment. There should be a redefinition of safety and efficacy respecting common sense, ie most MSsers should see clear improvement or symptomatic relief from a candidate drug. It is clear that raising the expectations would send most drugs out of the market, but at the same time stir more research. Of course, if a drug has been around for some time, has been proven literally safe and is cheap, it should be prescribed freely without the need of new trials".

Team G reposte. On this latter point I think Sir Jeremy would disagree, who maintains we need to show efficacy. Prof G thinks we need the Big pharma alternative and ensure we have the capacity to licence drugs before doing these studies.

Question 4.When I was diagnosed 10 years ago, stem cells therapies were talked about as offering a potential cure for MS. The hype has died down and I don't see much mention of repair in MS research. Is there much research looking at repair, not just to myelin, but to lost nerves? (Q posted 23rd Nov.2012). Did you miss it? Click here,

VV Response. "Repair is science-fiction. Millions of car accident victims need it as much as MSsers. Talking about repair in MS, without knowledge of the cause is fighting windmills with your mind".

Team G reposte. Mouse Doc and VV may have a similar view to the former at the moment and VV has a similar view to prof G on the latter. However, Sir Jeremy thinks we have come a long way without knowing the cause.

Question 5.Is a vitamin D deficit a cause or an effect of MS? (Q posted 4 December 2012). Did you miss it? Click here.

VV Response "The effect of chronic inflammation. The elephant in the room".

Team G reposte. DoctorRuth may have been gagging for a fight

Question 6."Is the use of a low fat diet,meditation and exercise important in improving the prognosis of MS? (Q Posted 4th Dec. 2012).Did you miss it? Click here

VV Response. "Exercise can at times make things worse, meditation might offer some symptomatic relief, low fat diet is the most promising approach".

Team G reposte. There would be a healthy debate here, with abit of agreement, some disagreement and some head scratching hoping for information to answer the question

Question 7.Will there be a cure for ms within the next 5-10 years? (Q.posted 29th Dec. 2012). Did you miss it? Click hereVV Response "MS can only be sufficiently treated in early patients. Permanent damage can not be reversed. Fortunately, MS can be treated now. Unfortunately, patients who choose to face their real problem have no support from neurologists or the health system. What is more they have to become researchers themselves".

Team G reposte. Would agree with VVs early thoughts and some think we may have the cure already, with the experiment ongoing. Others are more cautious, lets hope there are wrong and lets hope the future brings a reversal of the damage, there is a lot of effort doing on in that direction.There were a number of other questions that we did not have time to discuss, maybe we can do some of them. None of the panel except Prof B have seen VVs answers.

#MSBlog: As of the 2 January 2013 there have been 323 confirmed cases of natalizumab-associated PML.

"If you are on Natalizumab we would appreciate information about whether or not you are being monitored for PML using frequent MRI. The following survey is exploring this. Thanks."
Loading...CoI: multiple

OBJECTIVE: To create a reference table of disability outcomes in multiple sclerosis (MS) that would enable MSers to rank their disability relative to others' with similar disease duration and to develop a cost-effective research tool for comparing MS severity across MSer populations and time periods.

METHODS: The North American Research Committee on Multiple Sclerosis (NARCOMS) Registry collects disability data from MSers on a validated, 9-point Patient-Determined Disease Steps (PDDS) scale. The investigators' compiled the Disability Expectancy Table, which displays cumulative frequencies of PDDS scores for each year of disease duration, from 0 to 45 years. They also tabulated disease duration-adjusted mean ranks of PDDS scores, referred to as Patient-derived MS Severity Scores (P-MSSS).

RESULTS: The cohort consisted of 27,918 NARCOMS enrollees, 72.7% of whom were female and 90.1% of whom were white. Mean age at symptom onset was 30.1 ± 10.1 years, and age at enrollment was 47.1 ± 11.0 years. The Disability Expectancy Table and P-MSSS afford a detailed overview of disability outcomes in a large MS cohort over a 45-year period. In the first year of disease, 15% of MSers reported need of ambulatory aid, and 4% needed bilateral assistance or worse; after 45 years of disease, 76% of MSers required ambulatory aid, and 52% bilateral assistance or worse. Proportion of MSers who reported minimal or no interference in daily activities (PDDS ≤ 1) declined from 63% in the first year to 8% after 45 years of disease.

CONCLUSION: The Disability Expectancy Table allows individual patients to determine how their disability ranks relative to NARCOMS enrollees with the same disease duration. P-MSSS may be used to compare disability across MSer populations and to track disease progression in MSer cohorts. P-MSSS does not require a formal neurologic examination and may therefore find wide applicability as a practical and cost-effective outcome measure in epidemiologic studies.

"The concept in this study has already been done with the EDSS and is called the MS Severity Scale (MSSS). The advantage of this scale is that it will potentially allow MSers to work-out their own level of disability using a patient-related outcome (PRO) or outcome measure (PROM) and to compare it the course of a population is similar MSers. This will tell you if you disease rapid your disability is progressing. Knowing if you have benign or malignant disease will allow you to make better informed treatment decisions; particularly in relation to more risky treatments. What do you think?"

We have got a new voodoo doll called "Hedgehog", so when the trolls and insults arrive rather than bite, we have been asked by Prof G to stick pins into it.

Therefore, for the time being, we will try to simply remove or ignore offending comments rather than respond....at least whilst we work out the Rules of Engagement. Best wishes......The Doormats.

On another issue we have been receiving alot of spam from "anonymous" and have had to turn on the "word recognition" feature on during posting to stop the robots. It was Dumpster (for the Brits that's a skip or the big waste bin) central in one post alone this morning. Mention a word and they are in like sharks.

For our American Readers a hedgehog is like a very small porcupine, but cuter. They roll into a ball when frightened.

Since Tysabri was developed there was a hope that we could find a chemical pill that works just like tysabri ad blocks white cells getting into the brain. In many animal studies they have not looked as good as using antibodies, but here we have firatrgrast. It has been tested in MS and is indeed not as effective as Tysabri in relation to the reduction in gadolinium enhancing lesions as reported last year.

In this study they looked in the cerebrospinal fluid and found that the number of white blood cells dropped but they were not absent. They suggest that this leaves enough immune survellence so that may be good in stopping the development of PML. However it also probably means it will be less effective at dealing with MS, which is sort of supported by previous MRI studies. The cell number in the blood increased because they were stuck there as they could not escape. Is this going to be a safer alternative to tysabri? we will have to wait for phase III studies.

Sunday, 24 February 2013

"Google Glass is the next gizmo that will be arriving from Google. I can think of a dozen ways that it could help improve MSers lives. If you are a developer and want to do something for MSers please drop me a line. Thanks."

OBJECTIVE: A double-blind, randomized, controlled study to determine if combined use of interferon beta-1a (IFN) 30ug IM weekly and glatiramer acetate (GA) 20mg daily is more efficacious than either agent alone in relapsing-remitting multiple sclerosis (RRMS).

METHODS: 1008 participants were randomized and followed until the last participant enrolled completed 3 yrs. The primary endpoint was reduction in annualized relapse rate utilizing a strict definition of relapse. Secondary outcomes included time to confirmed disability, Multiple Sclerosis Functional Composite (MSFC) score and MRI metrics.

RESULTS: Combination IFN + GA was not superior to the better of the single agents (GA) in risk of relapse. Both the combination therapy and GA were significantly better than IFN in reducing the risk of relapse. The Combination was not better than either agent alone in lessening confirmed EDSS progression or change in MSFC over 36 months. The combination was superior to either agent alone in reducing new lesion activity and accumulation of total lesion volumes. In a post hoc analysis, combination therapy resulted in a higher proportion of participants attaining disease activity free status (DAFS) compared to either single arm; driven by the MRI results.

INTERPRETATION: Combining the two most commonly prescribed therapies for MS did not produce a significant clinical benefit over three years. An effect was seen on some MRI metrics. In a test of comparative efficacy, GA was superior to IFN in reducing the risk of exacerbation. The extension phase for CombiRx will address if the observed differences in MRI and DAFS findings predict later clinical differences.

Combining beta interferon with glatiramer acetate (Copaxone) does not appear to add any benefit over either one alone. This is sort of disturbing because if they really have different mechanisms as could be inferred, you would have hoped that they would have some additive effect, but apparently not so.

Epub: Miller et al. Evaluation of the effects of reflexology on quality of life and symptomatic relief in multiple sclerosis patients with moderate to severe disability; a pilot study. Clin Rehabil. 2013 Feb.Objective: To examine the feasibility of delivering reflexology to people moderately to severely affected by multiple sclerosis and to investigate the effect on a range of symptoms.Methods: A pilot single-blind randomized placebo controlled trial was conducted. Twenty people moderately to severely affected by multiple sclerosis were randomized into one of two groups receiving either reflexology or sham reflexology. Each participant received 8 weeks, 1 hour per week of either reflexology or sham reflexology. The primary outcome measure was the Multiple Sclerosis Impact Scale (MSIS29). Secondary measures assessed a range of symptoms at baseline, 8 weeks and 16 weeks.

Results: There were no statistically significant differences between the two groups at either 8 (P = 0.538) or 16 (P = 0.112) weeks for the primary outcome measure; however, both groups demonstrated small improvements from 92.3 (SD 20.9) to 75.6 (SD 3.3) with reflexology, and 91.3 (SD 29.9) to 81.5 (±18.5) with sham reflexology group after 8 weeks of treatment. Small improvements were noted in most of the secondary outcome measures at 8 weeks. There was no difference between the groups at 8 weeks except for bladder function (P = 0.003) and most scores returned to baseline at follow-up.

Conclusions: The results do not support the use of reflexology for symptom relief in a more disabled multiple sclerosis population and are strongly suggestive of a placebo response. This study demonstrates, however, that reflexology can be delivered and is well tolerated by people who are moderately to severely affected by multiple sclerosis.

This study examined the use of reflexology and which is the application of pressure to areas of the body such as the feet, etc. with hands, fingers etc. without the use of oil. This study indicates that it does not do much for symptom relief. However, the study was small and was it really powered enough to show a difference. So no doubt we we will see another underpowered study in the future not telling us much definative. So if it it makes you feel better that's great and enjoy the experience but there is nothing to indicate that it does anything medically.

Background: Natalizumab is a monoclonal antibody that prevents inflammatory cells from binding to brain endothelial cells and passing into the brain parenchyma. Natalizumab is a highly effective treatment for relapsing-remitting multiple sclerosis (MS). Progressive multifocal leukoencephalopathy (PML) is an opportunistic brain JC virus infection that has been shown to be associated with natalizumab treatment.

Case report: This is a report of PML in an MSers after 44 monthly infusions of natalizumab. With the aid of a routine Magnetic resonance imaging (MRI) scan, PML was detected before any unambiguous clinical manifestations had emerged. PML was then treated with plasma exchange to accelerate removal of natalizumab. Mirtazapine and mefloquine was promptly added and approximately 1 month after plasma exchange, when an immune-reconstitution-inflammatory-syndrome appeared, steroid treatment was initiated. Steroid treatment was then continued until no virus could be detected in the cerebrospinal fluid. The outcome was favorable.

Conclusion: This case clearly illustrates the importance of an early, presymptomatic, detection of PML, and an adequate treatment. The authors' also propose that surveillance with MRI scans, every 3 months after 24 months of treatment, should be performed in JC virus antibody positive natalizumab-treated MSers in order to detect PML in an early phase."This case report illustrates that early detection and treatment of PML can result in a good prognosis for MSers on natalizumab. However, the recommendation that 3 monthly MRIs is the way to do this is premature. This strategy will need to be studied formerly in a prospective study to see if it works and is cost-effective. In the NHS, and other resource-restricted healthcare systems, MRIs are expensive and as a result restricted. Simply scanning someone every 3 months, without data to support this practice, is not feasible. At the moment we scan JCV-serpositive MSers on natalizumab annually and JCV-seronegative MSers every 2 years. Why? We do this to re-baseline them in case they develop a complication on natalizumab. A new baseline scan provides you with something to compare a new scan in the future with. Why do we do this? When MSers start natalizumab their scans usually change; i.e. some lesions regress or even disappear. In addition there is some pseudoatrophy; this refers to the phenomenon of the brain shrinking when inflammation resolves. All these factors change the way the scans look and this makes it difficult for a neuroradiologist to report new or atypical lesions that could be due PML."

"The question of whether or not we should scan JCV-positive MSers on natalizumab more frequently than annually, is an important one. if you are on natalizumab could you please answer this survey below to see what is happening to you and to see how practice varies across the world? If you know other MSers on natalizumab can you please forward them the link to this post. For this survey to be meaningful we need at least 50 respondents from your country."

OBJECTIVE: To evaluate the presence of chronic cerebrospinal venous
insufficiency (CCSVI) and cerebral venous anomalies in a consecutive series of
patients with multiple sclerosis (MS), other neurologic diseases (NEU) and healthy
controls (HC).

METHODS: A consecutive series of 80 MS patients, 41 HC and 40 NEU cases
underwent a transcranial and extracranial echo-color Doppler (ECD) evaluation
of cerebrospinal venous return in a sonographer-blinded fashion. According to
the original Dr. Zamboni's protocol, CCSVI was diagnosed in presence of ≥2 ECD
venous criteria.

RESULTS: We did not observe any association between CCSVI and MS. CCSVI
was detected in 17.5% of MS cases, 7.3% of HC and 11.5% of NEU patients
(p=0.333). The prevalence of internal jugular vein stenosis (IJV) and the
proportion of patients with any positive ECD criterion differed significantly
among groups, being higher in MS cases versus HC (67.5% and 76.2% versus 48.8%
and 41.5%, respectively; p=0.005 and p=0.006). No relationship between CCSVI
and MS type and severity was evidenced.

CONCLUSIONS: The present study argues against a positive link between
CCSVI and MS risk or severity. Interestingly, a weak association between venous
ECD anomalies (in particular IJV stenosis) and MS was observed in our
population. This finding should be interpreted with caution due to the possible
confounders and needs to be confirmed in large controlled studies.

More negative evidence for a causal role of CCSVI and MS, but more vascular
problems in MSers

METHODS: Single center, prospective case-control study of volunteer MS
and non-MS participants. A neurosonologist, blind to the subject's diagnosis,
used high resolution B-mode imaging with color and spectral Doppler to
systematically investigate, capture and record extracranial and intracranial
venous drainage. These neuroimaging results were evaluated and scored by an
expert blinded to subject's information and with no interactions with the
participants.

RESULTS: Altogether 276 subjects were studied: 206 with MS and 70
non-MS. MS patients were older than non-MS subjects (48.3±9.9 vs 44.3±11.8
years, p<0.007), with durations from first symptoms and diagnosis of 13.7±10
and 9.9±7.8 years, and EDSS 2.6±2.0. Overall, 82 subjects (29.7%) fulfilled one
of five NS criteria proposed for CCSVI; 13 (4.7%) fulfilled two criteria
required for diagnosis, none fulfilled >2 criteria. The distribution of
subjects with 0, 1 or 2 criteria did not differ significantly across all
diagnostic groupings, between MS and non-MS subjects, or within MS subgroups.
CCSVI was present in 7.14% of non-MS and 3.88% of MS patients (p=0.266). No
significant differences emerged between MS and non-MS subjects for extracranial
or intracranial venous flow rates.

INTERPRETATION: NS findings described as CCSVI are much less prevalent
than initially reported, and do not distinguish MS from other subjects. Our
findings do not support the hypothesis that CCSVI is causally associated with
MS.

BACKGROUND: Chronic Cerebrospinal Venous Insufficiency (CCSVI) has been
associated with multiple sclerosis (MS) with a risk ranging from as high as
two-hundred-fold to a protective effect. However, not all studies were blinded,
and the efficacy of blinding was never assessed.

OBJECTIVE: To evaluate the association of CCSVI with MS in a
cross-sectional blinded study and look for any association of CCSVI with the
severity of MS.

METHODOLOGY/PRINCIPAL FINDINGS: The Echo-color Doppler examination was
carried out in accordance with Zamboni's five criteria in 68 consecutive MS
patients and 68 healthy controls, matched by gender and age (±5 years). Four
experienced neurosonologists, blinded to the status of cases and controls,
performed the study and were then asked to guess the status (case or control)
of each participant. The number of positive CCSVI criteria was similar in the
two groups. CCSVI, defined as the presence of two or more criteria, was
detected in 21 cases (30.9%) and 23 controls (33.8%), with an OR of 0.9
(95%CL = 0.4-1.8, p = 0.71). The prevalence of CCSVI was related to age in
cases (OR increasing from 0.2 to 1.4), but not in controls. CCSVI positive
(N = 21) and negative (N = 47) MS patients were similar in clinical type, age
at disease onset, disability, and fatigue. Disease duration was longer
(16.5±9.8 years) in CCSVI positive than negative patients (11.5±7.4; p = 0.04).
The operators correctly guessed 34/68 cases (50%) and 45/68 controls (66%)
(p = 0.06), indicating a different success of blinding.

CONCLUSIONS/SIGNIFICANCE: CCSVI was not associated with MS itself, nor
its severity. We cannot rule out the possibility that CCSVI is a consequence of
MS or of aging. Blinding of sonographers is a key point in studying CCSVI and
its verification should be a requisite of future studies.

The conclusions say it all, Surely there is now enough evidence to say CCSVI
is not the cause of MS?

METHODS: We examined 146 MS patients, presenting with a clinically
isolated syndrome, relapsing-remitting, secondary progressive, or primary
progressive MS, and 38 healthy controls. Sonographic examination was performed
according to Zamboni's protocol and was performed by three independent
sonographers. The results of sonographic examination were compared with
clinical and demographic characteristics of the patients.

RESULTS: CCSVI, defined as the presence of at least two positive
Zamboni's criteria, was found in 76% of MS patients and 16% of control
subjects. B-mode anomalies of internal jugular veins, such as stenosis,
malformed valves, annuli, and septa were the most common lesions detected in MS
patients (80.8%) and controls (47.4%). We observed a positive correlation
between sonographic diagnosis of CCSVI and the patients' age (p=0.003).
However, such a correlation was not found in controls (p=0.635). Notably, no
significant correlations were found between sonographic signs of CCSVI and
clinical characteristics of MS, except for absent flow in the jugular veins,
which was found more often in primary (p<0.005) and secondary (p<0.05)
progressive patients compared with non-progressive patients. Absent flow in
jugular veins was significantly correlated with patients' age (p<0.0001).

CONCLUSIONS: Sonographically defined CCSVI is common in MS patients.
However, CCSVI appears to be primarily associated with the patient's age, and
poorly correlated with the clinical course of the disease.

Although it is debated whether chronic cerebro-spinal venous insufficiency
(CCSVI) plays a role in multiple sclerosis (MS) development, many patients
undergo endovascular treatment (ET) of CCSVI. A study is ongoing in Italy to
evaluate the clinical outcome of ET. Severe adverse events (AEs) occurred in
15/462 subjects at a variable interval after ET: jugular thrombosis in seven
patients, tetraventricular hydrocephalus, stroke, paroxysmal atrial
fibrillation, status epilepticus, aspiration pneumonia, hypertension with
tachicardia, or bleeding of bedsore in the remaining seven cases. One patient
died because of myocardial infarction 10 weeks after ET. The risk of severe AEs
related to ET for CCSVI must be carefully considered.

As we have always said there can be consequences of having the CCSVI
procedure, it is not high but it is not trivial and the question remains, it is
an unproven therapy.

The American Academy of Neurologists Meeting 2013 Abstracts are
Published.

BACKGROUND: CCSVI is a hypothesis of MS pathogenesis related to venous outflow
from the head, with conflicting results from different studies. Recent studies
have found a very low prevalence of CCSVI, suggesting that those investigators
were performing ultrasound assessments differently than the original
reports.

DESIGN/METHODS: After obtaining formal training in CCSVI ultrasound techniques, we
performed ultrasound assessments on a group of 61 MS subjects (4 CIS, 28 RRMS,
19 SPMS, 10 PPMS; 42 females) and 20 non-MS controls (15 healthy and 5 other
neurological diseases; 10 female). Ultrasonographers were blinded to diagnosis,
and separate research staff positioned subjects prior to ultrasonographer
arrival. Assessments were performed using a Biosound MyLab25, equipped with
Quality Doppler Profiles (QDP) technology, and traditional transcranial
Doppler. Two published interpretations of CCSVI Criteria were utilized: Narrow
Criteria did not include either B-mode intraluminal abnormalities or QDP
technology for deep cerebral vein reflux, while Broad Criteria included both of
these.

RESULTS: Using either Narrow Criteria or Broad Criteria, there were no
significant differences between MS subjects and controls (p>0.5 for both
comparisons). In both groups, there was a doubling of the proportion of
subjects meeting CCSVI criteria when using the Broad Criteria.

CONCLUSIONS: Using trained and blinded ultrasonographers and QDP
technology, we observed no difference in the proportion of MS subjects meeting
CCSVI criteria compared to non-MS controls. Different interpretations of CCSVI
criteria altered the proportions of subjects meeting CCSVI criteria,
highlighting the importance of criteria interpretations when comparing the
prevalence of CCSVI between studies. These observations do not support a significantly
increased prevalence of CCSVI in MS and suggest against a pathogenic role of
CCSVI in MS.

OBJECTIVE: We aimed to describe the population of Multiple Sclerosis
(MS) patients reporting chronic cerebrospinal venous insufficiency (CCSVI)
treatment and to describe the change in treatment patterns and opinions over
time.

BACKGROUND: The CCSVI hypothesis has been of great interest to MS patients. Many
Albertans have travelled out-of-country for venous angioplasty.

DESIGN/METHODS: Initiated in July 2011, The Alberta Multiple Sclerosis Initiative is a
longitudinal observational study that uses online questionnaires to collect
patient-reported information about the safety, experiences, and outcomes
following CCSVI treatment. All Albertans with MS have been encouraged to
participate, irrespective of treatment status. Enrollment is ongoing.

RESULTS: This analysis included 733 participants. Mean (SD) age was 47.9 (11.2)
years, 76.5% were female, and 63.8% had relapsing remitting MS; 152
participants (20.7%; 95% CI: 17.9-23.9%) reported having CCSVI treatment,
beginning in March 2010. Participants were more likely to have undergone
treatment in 2010 (66.4%; 95% CI: 58.3-73.9%, n=101) than in 2011 (30.9 %; 95%
CI: 23.7-38.9%, n=47), even after controlling for the period of enrolment.
Between January and June 2012 only four participants had CCSVI treatment (2.6%;
95% CI: 0.7-6.6%). Older age, male sex, a progressive course, and greater
disability were more common in those who had CCSVI treatment.

CONCLUSIONS: The number of participants reporting CCSVI treatment is declining.
This may indicate that patients who wanted and could afford out-of-country
treatment went soon after the CCSVI hypothesis was widely publicized. However,
this may also reflect declining patient interest after they observed the
outcomes in this earlier group of patients. The sociodemographic and clinical
characteristics of participants who received CCSVI treatment will be compared
to those who did not receive treatment. Factors that influenced participants'
opinions for or against having CCSVI treatment will be compared over time

BACKGROUND: The chronic cerebrospinal venous insufficiency (CCSVI) hypothesis has
been proposed as the causal factor for MS. Contradictory data on the
association between CCSVI and MS have been reported to date. CCSVI was defined
as impaired extra cranial cerebrospinal venous drainage which leads to the
accumulation of cerebral iron deposits causing inflammation and degeneration.

DESIGN/METHODS: 82 eligible patients completed a questionnaire regarding changes in
their MS symptoms after ET including fatigue, sensory deficits, impairments in
mobility, coordination, bladder control and cognition. First, we examined
symptom changes within 2 weeks after treatment compared to before. For
longitudinal assessment, we divided patients to 3 groups; patients who had ET
1) within past 6 month 2) 6-12 months or 3) more than 12 months. Changes at the
time of interview were compared to those before the ET. Their EDSS score was
measured before and after ET and analyzed using student t test.

RESULTS: Within 2 weeks after treatment, 70% (56/79) reported decreased
fatigue. About two-thirds reported improvement in cognition (38/65), mobility
(51/79) and perceived warming in their limb temperature (40/63). Half of
patients reported improvement in bladder control (34/73), coordination (37/73)
and sensory deficits (28/61). Longitudinal assessment of symptoms revealed that
initial reported improvement in most symptoms greatly diminished over time.
Furthermore, we did not find any significant difference between EDSS scores
before and after the ET (P=0.828).

CONCLUSIONS: Our findings indicate that ET procedures for CCSVI are associated with
subjective reports of improvement of various symptoms by many patients without
any corresponding objective change in neurological evaluations as measured by
neurologist-derived EDSS scores. These uncontrolled and unblinded observations
do not provide any credible evidence of a true benefit from ET for MS.

You can read the conclusions!

However remember the cannabinoid trials there were subjective improvements
reported by MSers, but no objective benefits in spasticity scales. They changed
the way they do trials listened to MSers and Sativex was born

However I wonder whether the writing is on the wall with regard to the results
of the blinded trials?

Rationale: It is estimated that some hundreds of Canadian patients with multiple
sclerosis (MS) have journeyed abroad to avail themselves of 'liberation
therapy' (venoplasty) following the initial report by Zamboni et al in 2009.
That study also led to public pressure upon Departments of Health in Canadian
Provinces to fund the procedure. The present study was done in order to advise
the Government of Newfoundland and Labrador as to whether or not it should do
so.

Methods: We conducted an observational study of 30 MS subjects who had
submitted to venoplasty, using objective, semi-objective and subjective
measures.

Results: Significant subjective improvement was reported by half of the
subjects at three months, although the degree of perceived improvement was less
at 12 months. The objective and semi-objective tests employed did not indicate
improvement in any area over the one-year follow-up period. Seven of the 29
subjects in whom CT venography was performed at the end of the study year were
found to have uni- or bilateral occlusion or >50% stenosis of at least one
cervical draining vein, but they showed no deterioration in their clinical status
compared to those in whom no venous occlusion nor stenosis was found.

Conclusion: No objective improvement was found at one year in thirty MS
subjects who had undergone venoplasty, although many reported a degree of
subjective benefit.

This study offers some encouragement in that some improvements are felt
after venoplasty but the effect was largely transient and was not seen by the
neuro. Restenosis was common. However is this a disaster zone for the Brave
Dreams trials? This I think is set to run that are set to run over 12 months.

BACKGROUND: In 2009, Dr. Paolo Zamboni proposed chronic cerebrospinal
venous insufficiency (CCSVI) as a possible cause ofmultiple sclerosis (MS).
Although his theory and the associated treatment ("liberation
therapy") received little more than passing interest in the international
scientific and medical communities, his ideas became the source of tremendous
public and political tension in Canada. The story moved rapidly from mainstream
media to social networking sites. CCSVI and liberation therapy swiftly garnered
support among patients and triggered remarkable and relentless advocacy
efforts. Policy makers have responded in a variety of ways to the public's call
for action.

DISCUSSION: We present three different perspectives on this evolving
story, that of a health journalist who played a key role in the media coverage
of this issue, that of a health law and policy scholar who has closely observed
the unfolding public policy developments across the country, and that of a
medical ethicist who sits on an expert panel convened by the MS Society of
Canada and the Canadian Institutes of Health Research to assess the evidence as
it emerges.

SUMMARY: This story raises important questions about resource allocation
and priority setting in scientific research and science policy. The growing
power of social media represents a new level of citizen engagement and
advocacy, and emphasizes the importance of open debate about the basis on which
such policy choices are made. It also highlights the different ways evidence
may be understood, valued and utilized by various stakeholders and further
emphasizes calls to improve science communication so as to support balanced and
informed decision-making.

An interesting read, it is open source so I will not spend time commenting
on this but take a few quotes as food for thought.

"In the end, one thing that journalism and science—two disparate
professions—have in common is that they are self-correcting over time. It’s not
always a pretty process but it is a necessary and informative one".

"The rapidity with which new findings, whether speculative or proven, make
their way into the public sphere has undergone a paradigm shift such that the
process in which “evidence” is manufactured may be changing irrevocably."

"Gone are the days when researchers and clinicians can rely on a few hours
of “media training” to prepare them for the off-chance they might be
interviewed about some aspect of their work........ the advent of the internet
and social media mean the ivory tower of academia might be stormed at any
moment by an interested, enthusiastic, and motivated public. Researchers and
clinicians must learn how to utilize these resources to ensure the message that
emerges is both balanced and informed."

This reminds me of the debate that Prof G lost on whether Academia should
engage with the Social Media!

PML Risk Infographic

Holistic Management of MS ver. 7.0

Search this Blog

Follow by Email

Subscribe To

Translate

Followers

Disclaimer

General Disclaimer: Please note that the opinions expressed here are those of the individual bloggers and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry, Queen Mary University of London or Barts Health NHS Trust.

Survey Disclaimer: No personal identifiers will be collected as part of these surveys. By completing these surveys you are consenting to the data you provide being analysed by Professors Giovannoni and Baker and their collaborators. Results of these surveys will be presented on this blog and may be submitted for publication.